Document Detail


Cytoprotective effect of bis(1-oxy-2-pyridinethiolato)oxovanadiun(IV) on myocardial ischemia/reperfusion injury elicits inhibition of Fas ligand and Bim expression and elevation of FLIP expression.
MedLine Citation:
PMID:  17658509     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
VO(OPT), bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), has been shown to increase tyrosine phosphorylation of proteins and promote the insulin receptor signaling, thereby elicit anti-diabetic action. We here investigated the cytoprotective action of VO(OPT) on myocardial infarction and cardiac functional recovery in rats subjected to myocardial ischemia/reperfusion and defined mechanisms underlying its cytoprotective action. Rats underwent 30 min myocardial ischemia by left anterior descending coronary artery occlusion followed by 24 h reperfusion. Post-ischemic treatment with VO(OPT) significantly reduced infarct size and improved cardiac function (left ventricular developed pressure and +/-dP/dt) after 72 h reperfusion and in a dose-dependent manner. Moreover, VO(OPT) treatment also dose-dependently significantly inhibited caspases-3, -9 and -7 processing, thereby elicited the anti-apoptotic effect. The cytoprotective effect of VO(OPT) was closely associated with restoration of Akt activity. The recovered Akt activity correlated with increased phosphorylation of Bad and forkhead transcription proteins, thereby inhibiting apoptotic signaling. Furthermore, treatment with VO(OPT) significantly increased FLIP expression, and decreased expression of Fas ligand and Bim in cardiomyocytes. Taken together, cardiomyocytes rescue following post-treatment with VO(OPT) from ischemia/reperfusion injury was mediated by increased FLIP expression and decreased Fas ligand and Bim expression via activation of Akt. These results demonstrate that treatment with VO(OPT) exerts significant cytoprotective effects along with improvement of cardiac functional recovery.
Authors:
Md Shenuarin Bhuiyan; Masatoshi Shibuya; Norifumi Shioda; Shigeki Moriguchi; Jiro Kasahara; Yosiharu Iwabuchi; Kohji Fukunaga
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-09
Journal Detail:
Title:  European journal of pharmacology     Volume:  571     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-17     Completed Date:  2007-10-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  180-8     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Apoptosis Regulatory Proteins / metabolism*
Blood Pressure / drug effects
CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
Cardiotonic Agents / pharmacology*,  therapeutic use
Caspases / antagonists & inhibitors,  metabolism
Coronary Vessels / surgery
Cytoprotection*
Disease Models, Animal
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Fas Ligand Protein / metabolism*
Forkhead Transcription Factors / metabolism
Ligation
Male
Membrane Proteins / metabolism*
Myocardial Infarction / etiology,  metabolism,  pathology,  physiopathology,  prevention & control*
Myocardial Ischemia / complications,  drug therapy,  metabolism
Myocardial Reperfusion Injury / etiology,  metabolism,  pathology,  physiopathology,  prevention & control*
Organometallic Compounds / pharmacology*,  therapeutic use
Phosphorylation
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects
Ventricular Function, Left / drug effects
Ventricular Pressure / drug effects
bcl-Associated Death Protein / metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bad protein, rat; 0/Bcl-2-like protein 11; 0/CASP8 and FADD-Like Apoptosis Regulating Protein; 0/Cardiotonic Agents; 0/Enzyme Inhibitors; 0/Fas Ligand Protein; 0/Forkhead Transcription Factors; 0/Membrane Proteins; 0/Organometallic Compounds; 0/Proto-Oncogene Proteins; 0/bcl-Associated Death Protein; 0/bis(1-oxy-2-pyridinethiolato)oxovanadium(IV); EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/Caspases

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